title: The pitfalls of profoundly effective analgesic therapies.
abstract: OBJECTIVE
  In essentially all areas of pain medicine, treatments with improved effectiveness are needed. Though gains have been made in recent years, suffering from acute postoperative pain, low back pain, cancer-related pain, and pain from other causes remains problematic. On the other hand, both science and industry are approaching the problem with ever more sophisticated techniques. Though not currently in our armamentarium, it seems likely that at some point we will be faced with the situation where profoundly effective broad-spectrum analgesic therapies are available to our patients. Depending on their mechanisms of action, there may be significant downsides to the use of these new medications. The objective of this report was to explore the consequences of developing profoundly effective analgesic agents.
  
  
  METHODS
  This report reviews some of the recent advancements in our march toward developing profoundly effective analgesics and some of the pitfalls we might anticipate will be associated with these agents. Specifically, the issue of pain as an essential protective mechanism is explored. The causes and consequences of inherited neuropathies associated with pain insensitivity are reviewed.
  
  
  RESULTS
  The ability to appreciate internal and external stimuli as painful is critical to humans. The loss of this ability has profound adverse consequences which in their extreme can be life threatening. Significant social issues might arise from the availability of profoundly effective analgesics. A structure for managing the introduction of these agents into clinical practice is suggested.
  
  
  CONCLUSIONS
  By anticipating the likely clinical properties of profoundly effective analgesics we place ourselves in best position to guide their development, assure their safety, and oversee their use. The early collaboration of industry, scientists, clinicians, and regulatory authorities may be the best course.
authors.affiliation: Department of Anesthesia, Stanford University School of Medicine, Stanford, CA, USA. djclark@stanford.edu
authors.forename: John David
authors.initials: JD
authors.lastname: Clark
mesh_terms: D000700:Analgesics / Q000627:therapeutic use*; D009477:Hereditary Sensory and Autonomic Neuropathies / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement / Q000379:methods; D011788:Quality of Life
chemical_list: D000700:Analgesics